Abstract
Old World monkey TRIM5alpha proteins are known to block the replication of human immunodeficiency virus and other retroviruses in a species-specific fashion. In this report, we show that specific forms of simian TRIM5alpha proteins can restrict herpes simplex virus (HSV) infection. To define the effect of TRIM5alpha on HSV replication, we examined HSV infection in HeLa cell lines that stably express simian and human orthologs of TRIM5alpha proteins. We demonstrated that several simian TRIM5alpha proteins can restrict HSV replication, with the TRIM5alpha protein of rhesus macaques showing the strongest inhibition of HSV infection. We also found that the level of the inhibition of virus replication was viral strain-specific. TRIM5alpha is likely to inhibit HSV at the early stage of infection; however, at later times of infection, the levels of TRIM5alpha are significantly decreased. Thus, some TRIM5alpha proteins exhibit antiviral effects that extend beyond retroviral infections, but HSV may be able to reduce this restriction by reducing TRIM5alpha levels during the later phases of virus replication. Our results also argue that TRIM5alpha is only part of the reduced level of HSV replication in rhesus macaques, which are known to be less susceptible to HSV infection than other primates.